MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease

Background: MicroRNA-455-3p is one of the highly conserved miRNAs involved in multiple cellular functions in humans and we explored its relevance to learning and memory functions in Alzheimer's disease (AD). Our recent in vitro studies exhibited the protective role of miR-455-3p against AD toxi...

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Autores principales:	Subodh Kumar, Hallie Morton, Neha Sawant, Erika Orlov, Lloyd E Bunquin, Jangampalli Adi Pradeepkiran, Razelle Alvir, P. Hemachandra Reddy
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Alzheimer's disease MicroRNA-455-3p Mouse models Mitochondrial biogenesis Synaptic activity Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/161c786904e942199dc7356a1efd7a32
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spelling	oai:doaj.org-article:161c786904e942199dc7356a1efd7a322021-11-14T04:32:42ZMicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease2213-231710.1016/j.redox.2021.102182https://doaj.org/article/161c786904e942199dc7356a1efd7a322021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2213231721003426https://doaj.org/toc/2213-2317Background: MicroRNA-455-3p is one of the highly conserved miRNAs involved in multiple cellular functions in humans and we explored its relevance to learning and memory functions in Alzheimer's disease (AD). Our recent in vitro studies exhibited the protective role of miR-455-3p against AD toxicities in reducing full-length APP and amyloid-β (Aβ) levels, and also in reducing defective mitochondrial biogenesis, impaired mitochondrial dynamics and synaptic deficiencies. In the current study, we sought to determine the function of miR-455-3p in mouse models. Methods: For the first time we generated both transgenic (TG) and knockout (KO) mouse models of miR-455-3p. We determined the lifespan extension, cognitive function, mitochondrial biogenesis, mitochondrial dynamics, mitochondrial morphology, dendritic spine density, synapse numbers and synaptic activity in miR-455-3p TG and KO mice. Results: MiR-455-3p TG mice lived 5 months longer than wild-type (WT) counterparts, whereas KO mice lived 4 months shorter than WT mice. Morris water maze test showed improved cognitive behavior, spatial learning and memory in miR-455-3p TG mice relative to age-matched WT mice and miR-455-3p KO mice. Further, mitochondrial biogenesis, dynamics and synaptic activities were enhanced in miR-455-3p TG mice, while these were reduced in KO mice. Overall, overexpressed miR-455-3p in mice displayed protective effects, whereas depleted miR-455-3p in mice exhibited deleterious effects in relation to lifespan, cognitive behavior, and mitochondrial and synaptic activities. Conclusion: Both mouse models could be ideal research tools to understand the molecular basis of aging and its relevance to AD and other age-related diseases.Subodh KumarHallie MortonNeha SawantErika OrlovLloyd E BunquinJangampalli Adi PradeepkiranRazelle AlvirP. Hemachandra ReddyElsevierarticleAlzheimer's diseaseMicroRNA-455-3pMouse modelsMitochondrial biogenesisSynaptic activityMedicine (General)R5-920Biology (General)QH301-705.5ENRedox Biology, Vol 48, Iss , Pp 102182- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer's disease MicroRNA-455-3p Mouse models Mitochondrial biogenesis Synaptic activity Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	Alzheimer's disease MicroRNA-455-3p Mouse models Mitochondrial biogenesis Synaptic activity Medicine (General) R5-920 Biology (General) QH301-705.5 Subodh Kumar Hallie Morton Neha Sawant Erika Orlov Lloyd E Bunquin Jangampalli Adi Pradeepkiran Razelle Alvir P. Hemachandra Reddy MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease
description	Background: MicroRNA-455-3p is one of the highly conserved miRNAs involved in multiple cellular functions in humans and we explored its relevance to learning and memory functions in Alzheimer's disease (AD). Our recent in vitro studies exhibited the protective role of miR-455-3p against AD toxicities in reducing full-length APP and amyloid-β (Aβ) levels, and also in reducing defective mitochondrial biogenesis, impaired mitochondrial dynamics and synaptic deficiencies. In the current study, we sought to determine the function of miR-455-3p in mouse models. Methods: For the first time we generated both transgenic (TG) and knockout (KO) mouse models of miR-455-3p. We determined the lifespan extension, cognitive function, mitochondrial biogenesis, mitochondrial dynamics, mitochondrial morphology, dendritic spine density, synapse numbers and synaptic activity in miR-455-3p TG and KO mice. Results: MiR-455-3p TG mice lived 5 months longer than wild-type (WT) counterparts, whereas KO mice lived 4 months shorter than WT mice. Morris water maze test showed improved cognitive behavior, spatial learning and memory in miR-455-3p TG mice relative to age-matched WT mice and miR-455-3p KO mice. Further, mitochondrial biogenesis, dynamics and synaptic activities were enhanced in miR-455-3p TG mice, while these were reduced in KO mice. Overall, overexpressed miR-455-3p in mice displayed protective effects, whereas depleted miR-455-3p in mice exhibited deleterious effects in relation to lifespan, cognitive behavior, and mitochondrial and synaptic activities. Conclusion: Both mouse models could be ideal research tools to understand the molecular basis of aging and its relevance to AD and other age-related diseases.
format	article
author	Subodh Kumar Hallie Morton Neha Sawant Erika Orlov Lloyd E Bunquin Jangampalli Adi Pradeepkiran Razelle Alvir P. Hemachandra Reddy
author_facet	Subodh Kumar Hallie Morton Neha Sawant Erika Orlov Lloyd E Bunquin Jangampalli Adi Pradeepkiran Razelle Alvir P. Hemachandra Reddy
author_sort	Subodh Kumar
title	MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease
title_short	MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease
title_full	MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease
title_fullStr	MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease
title_full_unstemmed	MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease
title_sort	microrna-455-3p improves synaptic, cognitive functions and extends lifespan: relevance to alzheimer's disease
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/161c786904e942199dc7356a1efd7a32
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MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease

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